Title: | Patient-derived tumor organoids mimic treatment-induced DNA damage response in glioblastoma |
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Authors: | ID Majc, Bernarda (Author) ID Habič, Anamarija (Author) ID Malavolta, Marta (Author) ID Vittori, Miloš (Author) ID Porčnik, Andrej (Author) ID Bošnjak, Roman (Author) ID Mlakar, Jernej (Author) ID Matjašič, Alenka (Author) ID Zupan, Andrej (Author) ID Skoblar Vidmar, Marija (Author) ID Lah Turnšek, Tamara (Author) ID Sadikov, Aleksander (Author) ID Breznik, Barbara (Author) ID Novak, Metka (Author) |
Files: | URL - Source URL, visit https://doi.org/10.1016/j.isci.2024.110604
PDF - Presentation file, download (9,14 MB) MD5: 220C2B909461DA4CB74BE4BD247ADC6C
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Language: | English |
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Typology: | 1.01 - Original Scientific Article |
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Organization: | NIB - National Institute of Biology
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Abstract: | Glioblastoma (GB) is the most common primary malignant brain tumor, characterized by resistance to therapy. Despite aggressive treatment options, GB remains an incurable disease. Invasiveness and heterogeneity are key GB features that cannot be studied in preclinical in vitro models. In this study, we investigated the effects of standard therapy using patient-derived GB organoids (GBOs). GBOs reflect the complexity and heterogeneity of the original tumor tissue. No significant effect on GBO viability or invasion was observed after irradiation and temozolomide treatment. E3 ubiquitin-protein ligase (MDM2), cyclin-dependent kinase inhibitor 1A (CDKN1A), and the serine/threonine kinases ATM and ATR were upregulated at the gene and protein levels after treatment. Our results show that the p53 pathway and DNA-damage response mechanisms were triggered, suggesting that GBOs recapitulate GB therapy resistance. GBOs thus provide a highly efficient platform to assess the specific responses of GB patients to therapy and to further explore therapy resistance. |
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Keywords: | cellular physiology, cellular toxicology, in vitro toxicology including 3D culture, technical aspects of cell biology, cancer |
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Publication status: | Published |
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Publication version: | Version of Record |
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Publication date: | 20.09.2024 |
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Year of publishing: | 2024 |
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Number of pages: | str. 1-19 |
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Numbering: | iss. 9, [art. no.] ǂ110604 |
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PID: | 20.500.12556/DiRROS-20412 |
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UDC: | 576 |
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ISSN on article: | 2589-0042 |
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DOI: | 10.1016/j.isci.2024.110604 |
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COBISS.SI-ID: | 205414147 |
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Note: | Soavtorji: Anamarija Habič, Marta Malavolta, Miloš Vittori, Andrej Porčnik, Roman Bošnjak, Jernej Mlakar, Alenka Matjašič, Andrej Zupan, Marija Skoblar Vidmar, Tamara Lah Turnšek, Aleksander Sadikov, Barbara Breznik, Metka Novak;
Nasl. z nasl. zaslona;
Opis vira z dne 27. 8. 2024;
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Publication date in DiRROS: | 09.09.2024 |
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Views: | 353 |
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Downloads: | 163 |
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